Metabolic comorbidities and the association with risks of recurrent metastatic disease in breast cancer survivors

Anwar S.L., Cahyono R., Prabowo D., Avanti W.S., Choridah L., Dwianingsih E.K., Harahap W.A., Aryandono T.

Division of Surgical Oncology – Department of Surgery, Dr. Sardjito Hospital / Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Jl. Kesehatan No. 1, Yogyakarta, 55281, Indonesia; Department of Radiology, Dr. Sardjito Hospital/Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia; Department of Anatomical Pathology, Dr. Sardjito Hospital / Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia; Division of Surgical Oncology, Dr. M Jamil Hospital / Faculty of Medicine, Universitas Andalas, Padang, 25127, Indonesia


Abstract

Background: Obesity and other metabolic comorbidities affect over 10% of patients with breast cancer and are closely related with adverse outcomes. Although metabolic comorbidities among breast cancer patients in low- and middle-income countries are suggested to be lower, only a few studies are currently available. Effective management of metabolic comorbidities in cancer patients has been associated with better outcomes. Methods: Non-metastatic breast cancer patients (N = 1081) treated in our department (2014–2018) were monitored for the presence of high Body Mass Index (BMI), diabetes or glucose intolerance, dyslipidemia, and hypertension and the development of recurrent metastatic diseases during a median follow-up of 3.9 years. Results: Glucose intolerance, hypertension, dyslipidemia, and BMI ≥ 27.7 kg/m2 considered at risk for metabolic comorbidities were found in 26.5, 42.6, 27.7, and 23.3% of breast cancer patients, respectively. Diabetes or glucose intolerance and having both glucose intolerance and dyslipidemia were associated with the risk of recurrent metastatic disease (OR = 1.442, 95%CI = 1.071–1.943, p = 0.016 and OR = 1.495, 95%CI = 1.090–2.049, p = 0.010; respectively). Having three or more metabolic comorbidities was significantly associated with the risk of recurrent metastatic disease (OR = 1.647, 95%CI = 1.139–2.382, p = 0.008) compared to patients without any comorbidity. The metabolic comorbidities were distributed unevenly among breast cancer subtypes. A significant association with recurrent metastatic disease was found in the Luminal B-like subtype. In post-menopausal patients, having more than three comorbidities was associated with a higher risk of recurrent metastatic disease compared to those without any comorbidity (OR = 2.000, 95%CI = 1.035–3.067, p = 0.001). The risks of having three or more metabolic comorbidities were significantly higher in breast cancer survivors who were obese, lived in an urban area, and received hormonal therapy of aromatase inhibitors. Conclusion: Metabolic comorbidities were frequently found in breast cancer patients and were associated with higher risks to develop recurrent metastatic disease, particularly in post-menopausal women. Subsequent larger studies are needed to better understand the association of metabolic comorbidities with patients’ quality of life and prognosis, and to explore the potential combination of clinical intervention and lifestyle modification in breast cancer survivors to treat as well as reduce their impact. © 2021, The Author(s).

Breast cancer; Diabetes; Dyslipidemia; Metabolic; Obesity


Journal

BMC Cancer

Publisher: BioMed Central Ltd

Volume 21, Issue 1, Art No 590, Page – , Page Count


Journal Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85106738335&doi=10.1186%2fs12885-021-08343-0&partnerID=40&md5=54f0c331c8ae5b69f8d65c0b2d965ee3

doi: 10.1186/s12885-021-08343-0

Issn: 14712407

Type: All Open Access, Gold, Green


References

Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R.L., Torre, L.A., Jemal, A., Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries (2018) CA Cancer J Clin, 68 (6), pp. 394-424; Pilleron, S., Sarfati, D., Janssen-Heijnen, M., Vignat, J., Ferlay, J., Bray, F., Soerjomataram, I., Global cancer incidence in older adults, 2012 and 2035: a population-based study (2019) Int J Cancer, 144 (1), pp. 49-58; Martei, Y.M., Pace, L.E., Brock, J.E., Shulman, L.N., Breast cancer in low- and middle-income countries (2018) Clin Lab Med, 38 (1), pp. 161-173; Dillekås, H., Rogers, M.S., Straume, O., Are 90% of deaths from cancer caused by metastases? (2019) Cancer Med, 8 (12), pp. 5574-5576; Jaacks, L.M., Vandevijvere, S., Pan, A., McGowan, C.J., Wallace, C., Imamura, F., The obesity transition: stages of the global epidemic (2019) Lancet Diabetes Endocrinol, 7 (3), pp. 231-240; Herningtyas, E.H., Ng, T.S., Prevalence and distribution of metabolic syndrome and its components among provinces and ethnic groups in Indonesia (2019) BMC Public Health, 19 (1), p. 377; Popkin, B.M., Corvalan, C., Grummer-Strawn, L.M., Dynamics of the double burden of malnutrition and the changing nutrition reality (2020) Lancet, 395 (10217), pp. 65-74; Kabat, G.C., Kim, M.Y., Lee, J.S., Ho, G.Y., Going, S.B., Beebe-Dimmer, J., Manson, J.A.E., Rohan, T.E., Metabolic obesity phenotypes and risk of breast cancer in postmenopausal women (2017) Cancer Epidemiol Biomark Prev, 12 (12), pp. 1730-1735; Zhang, P.H., Chen, Z.W., Lv, D., Xu, Y.Y., Gu, W.L., Zhang, X.H., Increased risk of cancer in patients with type 2 diabetes mellitus: a retrospective cohort study in China (2012) BMC Public Health, 7 (12), pp. 1415-1423; Gathirua-Mwangi, W.G., Song, Y., Monahan, P.O., Champion, V.L., Zollinger, T.W., Associations of metabolic syndrome and C-reactive protein with mortality from total cancer, obesity-linked cancers and breast cancer among women in NHANES III (2018) Int J Cancer, 43 (3), pp. 535-542; Dibaba, D.T., Ogunsina, K., Braithwaite, D., Akinyemiju, T., Metabolic syndrome and risk of breast cancer mortality by menopause, obesity, and subtype (2019) Breast Cancer Res Treat, 174 (1), pp. 209-218; Esposito, K., Chiodini, P., Capuano, A., Bellastella, G., Maiorino, M.I., Rafaniello, C., Giugliano, D., Metabolic syndrome and postmenopausal breast cancer: systematic review and meta-analysis (2013) Menopause, 20 (12), pp. 1301-1309; Ee, C., Cave, A.E., Naidoo, D., Bilinski, K., Boyages, J., Weight before and after a diagnosis of breast cancer or ductal carcinoma in situ: a national Australian survey (2020) BMC Cancer, 20 (1), p. 113; Thürlimann, B., Keshaviah, A., Coates, A.S., Mouridsen, H., Mauriac, L., Forbes, J.F., A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer (2005) N Engl J Med, 353 (26), pp. 2747-2757; Westerink, N.L., Nuver, J., Lefrandt, J.D., Vrieling, A.H., Gietema, J.A., Walenkamp, A.M.E., Cancer treatment induced metabolic syndrome: improving outcome with lifestyle (2016) Crit Rev Oncol Hematol, 108, pp. 128-136; Banegas, M.P., Dickerson, J.F., Kent, E.E., de Moor, J.S., Virgo, K.S., Guy, G.P., Exploring barriers to the receipt of necessary medical care among cancer survivors under age 65 years (2018) J Cancer Surviv, 12 (1), pp. 28-37; Picon-Ruiz, M., Morata-Tarifa, C., Valle-Goffin, J.J., Friedman, E.R., Slingerland, J.M., Obesity and adverse breast cancer risk and outcome: mechanistic insights and strategies for intervention (2017) CA Cancer J Clin, 67 (5), pp. 378-397; Calip, G.S., Malone, K.E., Gralow, J.R., Stergachis, A., Hubbard, R.A., Boudreau, D.M., Metabolic syndrome and outcomes following early-stage breast cancer (2014) Breast Cancer Res Treat, 148 (2), pp. 363-377; Edge, S.B., Comptom, C.C., American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM (2010) Ann Surg Oncol, 17 (6), pp. 1471-1474; Sinn, H.P., Kreipe, H., A brief overview of the WHO classification of breast tumors, 4th edition, focusing on issues and updates from the 3rd edition (2013) Breast Care, 8 (2), pp. 149-154; Genestie, C., Zafrani, B., Asselain, B., Fourquet, A., Rozan, S., Validire, P., Comparison of the prognostic value of Scarff-Bloom-Richardson and Nottingham histological grades in a series of 825 cases of breast cancer: major importance of the mitotic count as a component of both grading systems (1998) Anticancer Res, 18 (1 B), pp. 571-576. , COI: 1:STN:280:DyaK1c3ivFKjsg%3D%3D, PID: 9568179; Goldhirsch, A., Winer, E.P., Coates, A.S., Gelber, R.D., Thürlimann, B., Panel, H.S., Personalizing the treatment of women with early breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013 (2013) Ann Oncol, 24 (9), pp. 2206-2223; Widodo, I., Dwianingsih, E.K., Anwar, S.L., Fx Ediati, T., Utoro, T., Aryandono, T., Prognostic value of clinicopathological factors for Indonesian breast carcinomas of different molecular subtypes (2017) Asian Pac J Cancer Prev, 18, pp. 1251-1256; Ul-Haq, Z., Mackay, D.F., Frenwick, E., Pell, J.P., Impact of metabolic comorbidity on the association between body mass index and health-related quality of life: a Scotland-wide cross-sectional study of 5,608 participants (2012) BMC Public Health, 12, p. 142; Hudson, S.E., Feigenbaum, M.S., Patil, N., Ding, E., Ewing, A., Trilk, J.L., Screening and socioeconomic associations of dyslipidemia in young adults (2020) BMC Public Health, 20 (1), p. 104; Berrino, F., Villarini, A., Traina, A., Bonanni, B., Panico, S., Mano, M.P., Mercandino, A., Pasanisi, P., Metabolic syndrome and breast cancer prognosis (2014) Breast Cancer Res Treat, 147 (1), pp. 159-165; Monzavi-Karbassi, B., Gentry, R., Kaur, V., Siegel, E.R., Jousheghany, F., Medarametla, S., Pre-diagnosis blood glucose and prognosis in women with breast cancer (2016) Cancer Metab, 4, p. 7; Bandera, E.V., Maskarinec, G., Romieu, I., John, E.M., Racial and ethnic disparities in the impact of obesity on breast cancer risk and survival: a global perspective (2015) Adv Nutr, 6 (6), pp. 803-819; Bjørge, T., Lukanova, A., Jonsson, H., Tretli, S., Ulmer, H., Manjer, J., Stocks, T., Engeland, A., Metabolic syndrome and breast cancer in the Me-Can (Metabolic Syndrome and Cancer) Project (2010) Cancer Epidemiol Biomark Prev, 19 (7), pp. 1737-1745; Zhang, M., Cai, H., Bao, P., Xu, W., Qin, G., Shu, X.O., Zheng, Y., Body mass index, waist-to-hip ratio and late outcomes: a report from the Shanghai breast cancer survival study (2017) Sci Rep, 7 (1), p. 6996; Simon, M.S., Beebe-Dimmer, J.L., Hastert, T.A., Manson, J.A.E., Cespedes Feliciano, E.M., Neuhouser, M.L., Ho, G.Y.F., Caan, B., Cardiometabolic risk factors and survival after breast cancer in the Women’s Health Initiative (2018) Cancer, 124 (8), pp. 1798-1807; Fan, Y., Ding, X., Wang, J., Ma, F., Yuan, P., Li, Q., Zhang, P., Xu, B., Decreased serum HDL at initial diagnosis correlates with worse outcomes for triple-negative breast cancer but not non-TNBCs (2015) Int J Biol Markers, 30 (2), pp. e200-e207; Perry, C.S., Otero, J.C., Palmer, J.L., Gross, A.S., Risk factors for breast cancer in East Asian women relative to women in the West (2009) Asia Pac J Clin Oncol, 5 (4). , (,)., https://doi.org/10.1111/j.1743-7563.2009.01242.x; Nam, S., Park, S., Park, H.S., Kim, S., Kim, J.Y., Kim, S.I., Association between insulin resistance and luminal B subtype breast cancer in postmenopausal women (2016) Medicine (Baltimore), 95 (9); Iyengar, P., Combs, T.P., Shah, S.J., Gouon-Evans, V., Pollard, J.W., Albanese, C., Flanagan, L., Scherer, P.E., Adipocyte-secreted factors synergistically promote mammary tumorigenesis through induction of anti-apoptotic transcriptional programs and proto-oncogene stabilization (2003) Oncogene, 22 (41), pp. 6408-6423; Gandhi, N., Das, G., Metabolic reprogramming in breast cancer and its therapeutic implications (2019) Cells, 8 (2), p. 89; Kosalka, P., Johnson, C., Turek, M., Sulpher, J., Law, A., Botros, J., Dent, S., Aseyev, O., Effect of obesity, dyslipidemia, and diabetes on trastuzumab-related cardiotoxicity in breast cancer (2019) Curr Oncol, 26 (3), pp. e314-e321; Bulun, S.E., Chen, D., Moy, I., Brooks, D.C., Zhao, H., Aromatase, breast cancer and obesity: a complex interaction (2012) Trends Endocrinol Metab, 23 (2), pp. 83-89; Mauvais-Jarvis, F., Clegg, D.J., Hevener, A.L., The role of estrogens in control of energy balance and glucose homeostasis (2013) Endocr Rev, 34 (3), pp. 309-338; Djiogue, S., Kamdje, A.H.N., Vecchio, L., Kipanyula, M.J., Farahna, M., Aldebasi, Y., Insulin resistance and cancer: the role of insulin and IGFs (2013) Endocr Relat Cancer, 20 (1), pp. R1-R17; Pierce, B.L., Ballard-Barbash, R., Bernstein, L., Baumgartner, R.N., Neuhouser, M.L., Wener, M.H., Baumgartner, K.B., Ulrich, C.M., Elevated biomarkers of inflammation are associated with reduced survival among breast cancer patients (2009) J Clin Oncol, 27 (21), pp. 3437-3444; Mantovani, A., Allavena, P., Sica, A., Balkwill, F., Cancer-related inflammation (2008) Nature, 454 (7203), pp. 436-444; Chiang, A.C., Massagué, J., Molecular basis of metastasis (2008) N Engl J Med, 359 (26), pp. 2814-2823; Santos, A.C., Ebrahim, S., Barros, H., Gender, socio-economic status and metabolic syndrome in middle-aged and old adults (2008) BMC Public Health, 8 (1), p. 62; Zhan, Y., Yu, J., Chen, R., Gao, J., Ding, R., Fu, Y., Zhang, L., Hu, D., Socioeconomic status and metabolic syndrome in the general population of China: a cross-sectional study (2012) BMC Public Health, 12 (1), p. 921; Jiralerspong, S., Kim, E.S., Dong, W., Feng, L., Hortobagyi, G.N., Giordano, S.H., Obesity, diabetes, and survival outcomes in a large cohort of early-stage breast cancer patients (2013) Ann Oncol, 24 (10), pp. 2506-2514; Davies, C., Pan, H., Godwin, J., Gray, R., Arriagada, R., Raina, V., Abraham, M., Peto, R., Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial (2013) Lancet, 381 (9869), pp. 805-816; Matthews, A., Stanway, S., Farmer, R.E., Strongman, H., Thomas, S., Lyon, A.R., Long term adjuvant endocrine therapy and risk of cardiovascular disease in female breast cancer survivors: systematic review (2018) BMJ (Online), 363, p. k3845; Braithwaite, D., Moore, D.H., Satariano, W.A., Kwan, M.L., Hiatt, R.A., Kroenke, C., Caan, B.J., Prognostic impact of comorbidity among long-term breast cancer survivors: results from the LACE study (2012) Cancer Epidemiol Biomark Prev, 21 (7), pp. 1115-1125; Fredslund, S.O., Gravholt, C.H., Laursen, B.E., Jensen, A.B., Key metabolic parameters change significantly in early breast cancer survivors: an explorative PILOT study (2019) J Transl Med, 17 (1), p. 105; Anwar, S.L., Raharjo, C.A., Herviastuti, R., Dwianingsih, E.K., Setyoheriyanto, D., Avanti, W.S., Choridah, L., Wulaningsih, W., Pathological profiles and clinical management challenges of breast cancer emerging in young women in Indonesia: a hospital-based study (2019) BMC Womens Health, 9 (1), p. 28; Heo, J., Chun, M., Oh, Y.T., Noh, O.K., Kim, L., Metabolic comorbidities and medical institution utilization among breast cancer survivors: a national population-based study (2020) Korean J Intern Med, 35 (2), pp. 421-428; Anwar, S.L., Tampubolon, G., Van Hemelrijck, M., Hutajulu, S.H., Watkins, J., Wulaningsih, W., Determinants of cancer screening awareness and participation among Indonesian women (2018) BMC Cancer, 18 (1), p. 208; Anwar, S.L., Adistyawan, G., Wulaningsih, W., Gutenbrunner, C., Nugraha, B., Rehabilitation for cancer survivors: how we can reduce the healthcare service inequality in low- and middle-income countries (2018) Am J Phys Med Rehabil, 97 (10), pp. 764-771; Schmitz, K.H., Campbell, A.M., Stuiver, M.M., Pinto, B.M., Schwartz, A.L., Morris, G.S., Ligibel, J.A., Matthews, C.E., Exercise is medicine in oncology: engaging clinicians to help patients move through cancer (2019) CA Cancer J Clin, 9 (6), pp. 468-484; Blanchard, C.M., Courneya, K.S., Stein, K., Cancer survivors’ adherence to lifestyle behavior recommendations and associations with health-related quality of life: results from the American Cancer Society’s SCS-II (2008) J Clin Oncol, 6 (13), pp. 2198-2204; Guidelines, P.A., American Cancer Society guidelines on nutrition and physical activity for cancer prevention summary of the ACS guidelines on nutrition and physical activity (2012) Am Cancer Soc, 62 (1), pp. 30-67; Dieli-Conwright, C.M., Mortimer, J.E., Schroeder, E.T., Courneya, K., Demark-Wahnefried, W., Buchanan, T.A., Tripathy, D., Bernstein, L., Randomized controlled trial to evaluate the effects of combined progressive exercise on metabolic syndrome in breast cancer survivors: rationale, design, and methods (2014) BMC Cancer, 14 (1), p. 238; Anwar, S.L., Avanti, W.S., Nugroho, A.C., Choridah, L., Dwianingsih, E.K., (2020) Risk factors of distant metastasis after surgery among different breast cancer subtypes: A hospital-based study in Indonesia, 18 (1), pp. 117-133; Anwar, S.L., Prabowo, D., Avanti, W.S., Dwianingsih, E.K., Harahap, W.A., Aryandono, T., Clinical characteristics and the associated risk factors of the development of bilateral breast cancers: a case-control study (2020) Ann Med Surg, 60, pp. 285-292

Indexed by Scopus

Leave a Comment